Molecular biomedicine最新文献

{"title":"G protein-coupled receptor 107 deficiency promotes development of diabetic nephropathy.","authors":"Deping Xu, Ziwen Tong, Ping Yang, Qiong Chen, Suhua Wang, Wei Zhao, Linzi Han, Yu Yin, Ruyue Xu, Min Zhang, Chunlin Cai, Deguang Wang, Dandan Zang, Guoling Zhou, Haisheng Zhou","doi":"10.1186/s43556-025-00250-1","DOIUrl":"https://doi.org/10.1186/s43556-025-00250-1","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is characterized by glomerular basement membrane (GBM) thickening, primarily due to the abnormal accumulation of collagen type IV (COL4) in the extracellular matrix (ECM) of podocytes. Podocytes endocytosis is crucial for maintaining COL4 balance and GBM integrity. Previous studies have shown that G protein-coupled receptor 107 (GPR107) facilitates clathrin-dependent transferrin internalization and recycling in murine embryonic fibroblast cells. Therefore, the aim of the study is to investigate the role of GPR107 in regulating COL4 balance within the podocytes ECM and its potential as a therapeutic target for DN. Here, we found a significant decrease in GPR107 expression in renal tissues from DN patients and streptozocin (STZ)-induced DN mice. Furthermore, GPR107-deficient mice with STZ-induced DN exhibited more severe kidney damage, marked by increased GBM thickening and COL4 accumulation. In vitro, GPR107 deficiency under high-glucose conditions promoted COL4 accumulation in the ECM of podocytes due to increased COL4 production and decreased COL4 degradation. Mechanistically, we demonstrated that GPR107 contributes to angiotensin II receptor type 1 (AT1R) internalization through clathrin-mediated endocytosis (CME) in podocytes. Therefore, GPR107 deficiency impairs AT1R internalization, leading to increased membrane-bound AT1R. This, in turn, activates the AT1R/Ca²⁺ signaling pathway to promote phosphorylation of cAMP-response element-binding protein (CREB), ultimately enhancing COL4 synthesis and inhibiting the expression of matrix metalloproteinase 2 (MMP-2). These findings shed light on new functions of GPR107 in DN and offer new insights into a therapeutic target for DN.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"10"},"PeriodicalIF":6.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of urine DNA Neuritin 1 methylation test for urothelial carcinoma detection.","authors":"Yucai Wu, Yanqing Gong, Liqun Zhou, Abai Xu, Xuesong Li","doi":"10.1186/s43556-025-00245-y","DOIUrl":"10.1186/s43556-025-00245-y","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"8"},"PeriodicalIF":6.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor microbiome: roles in tumor initiation, progression, and therapy.","authors":"Shengxin Zhang, Jing Huang, Zedong Jiang, Huan Tong, Xuelei Ma, Yang Liu","doi":"10.1186/s43556-025-00248-9","DOIUrl":"10.1186/s43556-025-00248-9","url":null,"abstract":"<p><p>Over the past few years, the tumor microbiome is increasingly recognized for its multifaceted involvement in cancer initiation, progression, and metastasis. With the application of 16S ribosomal ribonucleic acid (16S rRNA) sequencing, the intratumoral microbiome, also referred to as tumor-intrinsic or tumor-resident microbiome, has also been found to play a significant role in the tumor microenvironment (TME). Understanding their complex functions is critical for identifying new therapeutic avenues and improving treatment outcomes. This review first summarizes the origins and composition of these microbial communities, emphasizing their adapted diversity across a diverse range of tumor types and stages. Moreover, we outline the general mechanisms by which specific microbes induce tumor initiation, including the activation of carcinogenic pathways, deoxyribonucleic acid (DNA) damage, epigenetic modifications, and chronic inflammation. We further propose the tumor microbiome may evade immunity and promote angiogenesis to support tumor progression, while uncovering specific microbial influences on each step of the metastatic cascade, such as invasion, circulation, and seeding in secondary sites. Additionally, tumor microbiome is closely associated with drug resistance and influences therapeutic efficacy by modulating immune responses, drug metabolism, and apoptotic pathways. Furthermore, we explore innovative microbe-based therapeutic strategies, such as engineered bacteria, oncolytic virotherapy, and other modalities aimed at enhancing immunotherapeutic efficacy, paving the way for microbiome-centered cancer treatment frameworks.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"9"},"PeriodicalIF":6.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose tissue-derived microRNA-450a-5p induces type 2 diabetes mellitus by downregulating DUSP10.","authors":"Jiaojiao Zhu, Yanting Hou, Wei Yu, Jingzhou Wang, Xiaolong Chu, Xueting Zhang, Huai Pang, Dingling Ma, Yihan Tang, Menghuan Li, Chenggang Yuan, Jianxin Xie, Cuizhe Wang, Jun Zhang","doi":"10.1186/s43556-025-00247-w","DOIUrl":"10.1186/s43556-025-00247-w","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) has rapidly increased worldwide, emerging as the fifth leading cause of death. The treatment of T2DM is challenging due to the side effects of oral hypoglycemic drugs and the limited efficacy of long-term insulin therapy, which can lead to insulin resistance (IR). Consequently, there is significant in discovering new drugs that have minimal side effects and a pronounced hypoglycemic effect. In obesity, microRNA levels have been implicated in glucose metabolism disorders and T2DM, although many aspects remain unresolved. Here, we confirmed that visceral adipose tissue and serum microRNA-450a-5p content increased under obesity and T2DM, and it was significantly positively associated with fasting blood glucose, triglycerides, cholesterol, low-density lipoproteins-cholesterol levels of the subjects. In high-fat diet (HFD)-induced obese mice, microRNA-450a-5p expression was increased in the serum, liver, and white adipose tissue. Moreover, the adipose Dicer-knockout mouse model was constructed to identify adipose tissue as the main source of microRNA-450a-5p. microRNA-450a-5p could inactivate the insulin signal pathway by targeting the inhibited Dual Specificity Phosphatase 10 (DUSP10) and inducing IR and glucose metabolism disorders in vitro cultured hepatocytes and adipocytes. Additionally, microRNA-450a-5p was found to regulate DUSP10 expression and insulin signaling activity, influencing glucose tolerance and insulin sensitivity across various models, including normal diet, HFD-induced obese, adipose tissue-specific microRNA-450a-5p-knockout, and db/db mice. Furthermore, gallic acid might play a potential role in inhibiting glucose levels by decreasing microRNA-450a-5p expression. Thus, microRNA-450a-5p emerges as an attractive therapeutic target for addressing obesity, IR, and T2DM.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"7"},"PeriodicalIF":6.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcoidosis: molecular mechanisms and therapeutic strategies.","authors":"Danfeng Xu, Xiaohua Tao, Yibin Fan, Yan Teng","doi":"10.1186/s43556-025-00244-z","DOIUrl":"10.1186/s43556-025-00244-z","url":null,"abstract":"<p><p>Sarcoidosis, a multisystemic granulomatous disease with unknown etiology, is characterized by formation of noncaseating granulomas, which can affect all organs. Recent studies have made outstanding achievement in understanding the pathology, etiology, genetics, and immune dysregulation involved in granuloma formation of sarcoidosis. Antigen stimulation in genetically predisposed individuals enhances the phagocytic activity of antigen-presenting cells, including macrophages and dendritic cells. CD4 + T cells initiate dysregulated immune responses and secrete significant quantities of inflammatory cytokines, including interleukin (IL)-2 and interferon-gamma (IFN-γ), which play a crucial role in modulating the aggregation and fusion of macrophages to form granulomas. The current therapeutic strategies focus on blocking the formation and spread of granulomas to protect organ function and alleviate symptoms. The efficacy of traditional treatments, such as glucocorticoids and immunosuppressants, has been confirmed in the management of sarcoidosis. Promising therapeutic agents encompass inhibitors of cytokines, like those targeting tumor necrosis factor (TNF)-α, as well as inhibitors of signaling pathways, such as Janus kinase (JAK) inhibitors, which exhibit favorable prospects for application. Although there has been progress in the identification of biomarkers for the diagnosis, prognosis, activity and severity of sarcoidosis, specific and sensitive biomarkers have yet to be identified. This review outlines recent advancements in the molecular mechanisms and therapeutic strategies for the sarcoidosis.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"6"},"PeriodicalIF":6.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amelioration of radiation-induced skin injury by tetrahydrobiopterin: preclinical study and phase II trial.","authors":"Kemin Li, Bin Song, Rutie Yin, Shuyu Zhang","doi":"10.1186/s43556-025-00246-x","DOIUrl":"10.1186/s43556-025-00246-x","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"5"},"PeriodicalIF":6.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tuberculosis vaccines and therapeutic drug: challenges and future directions.","authors":"Yajing An, Ruizi Ni, Li Zhuang, Ling Yang, Zhaoyang Ye, Linsheng Li, Seppo Parkkila, Ashok Aspatwar, Wenping Gong","doi":"10.1186/s43556-024-00243-6","DOIUrl":"10.1186/s43556-024-00243-6","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a prominent global health challenge, with the World Health Organization documenting over 1 million annual fatalities. Despite the deployment of the Bacille Calmette-Guérin (BCG) vaccine and available therapeutic agents, the escalation of drug-resistant Mycobacterium tuberculosis strains underscores the pressing need for more efficacious vaccines and treatments. This review meticulously maps out the contemporary landscape of TB vaccine development, with a focus on antigen identification, clinical trial progress, and the obstacles and future trajectories in vaccine research. We spotlight innovative approaches, such as multi-antigen vaccines and mRNA technology platforms. Furthermore, the review delves into current TB therapeutics, particularly for multidrug-resistant tuberculosis (MDR-TB), exploring promising agents like bedaquiline (BDQ) and delamanid (DLM), as well as the potential of host-directed therapies. The hurdles in TB vaccine and therapeutic development encompass overcoming antigen diversity, enhancing vaccine effectiveness across diverse populations, and advancing novel vaccine platforms. Future initiatives emphasize combinatorial strategies, the development of anti-TB compounds targeting novel pathways, and personalized medicine for TB treatment and prevention. Despite notable advances, persistent challenges such as diagnostic failures and protracted treatment regimens continue to impede progress. This work aims to steer future research endeavors toward groundbreaking TB vaccines and therapeutic agents, providing crucial insights for enhancing TB prevention and treatment strategies.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"4"},"PeriodicalIF":6.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer vaccines: platforms and current progress.","authors":"Wanting Lei, Kexun Zhou, Ye Lei, Qiu Li, Hong Zhu","doi":"10.1186/s43556-024-00241-8","DOIUrl":"10.1186/s43556-024-00241-8","url":null,"abstract":"<p><p>Cancer vaccines, crucial in the immunotherapeutic landscape, are bifurcated into preventive and therapeutic types, both integral to combating oncogenesis. Preventive cancer vaccines, like those against HPV and HBV, reduce the incidence of virus-associated cancers, while therapeutic cancer vaccines aim to activate dendritic cells and cytotoxic T lymphocytes for durable anti-tumor immunity. Recent advancements in vaccine platforms, such as synthetic peptides, mRNA, DNA, cellular, and nano-vaccines, have enhanced antigen presentation and immune activation. Despite the US Food and Drug Administration approval for several vaccines, the full therapeutic potential remains unrealized due to challenges such as antigen selection, tumor-mediated immunosuppression, and optimization of delivery systems. This review provides a comprehensive analysis of the aims and implications of preventive and therapeutic cancer vaccine, the innovative discovery of neoantigens enhancing vaccine specificity, and the latest strides in vaccine delivery platforms. It also critically evaluates the role of adjuvants in enhancing immunogenicity and mitigating the immunosuppressive tumor microenvironment. The review further examines the synergistic potential of combining cancer vaccines with other therapies, such as chemotherapy, radiotherapy, and immune checkpoint inhibitors, to improve therapeutic outcomes. Overcoming barriers such as effective antigen identification, immunosuppressive microenvironments, and adverse effects is critical for advancing vaccine development. By addressing these challenges, cancer vaccines can offer significant improvements in patient outcomes and broaden the scope of personalized cancer immunotherapy.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"3"},"PeriodicalIF":6.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer.","authors":"Yixiang Gu, Ruifeng Yang, Yang Zhang, Miaomiao Guo, Kyle Takehiro, Ming Zhan, Linhua Yang, Hui Wang","doi":"10.1186/s43556-024-00239-2","DOIUrl":"10.1186/s43556-024-00239-2","url":null,"abstract":"<p><p>Cancer remains a leading cause of mortality globally and a major health burden, with chemotherapy often serving as the primary therapeutic option for patients with advanced-stage disease, partially compensating for the limitations of non-curative treatments. However, the emergence of chemotherapy resistance significantly limits its efficacy, posing a major clinical challenge. Moreover, heterogeneity of resistance mechanisms across cancer types complicates the development of universally effective diagnostic and therapeutic approaches. Understanding the molecular mechanisms of chemoresistance and identifying strategies to overcome it are current research focal points. This review provides a comprehensive analysis of the key molecular mechanisms underlying chemotherapy resistance, including drug efflux, enhanced DNA damage repair (DDR), apoptosis evasion, epigenetic modifications, altered intracellular drug metabolism, and the role of cancer stem cells (CSCs). We also examine specific causes of resistance in major cancer types and highlight various molecular targets involved in resistance. Finally, we discuss current strategies aiming at overcoming chemotherapy resistance, such as combination therapies, targeted treatments, and novel drug delivery systems, while proposing future directions for research in this evolving field. By addressing these molecular barriers, this review lays a foundation for the development of more effective cancer therapies aimed at mitigating chemotherapy resistance.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"2"},"PeriodicalIF":6.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of artificial intelligence in pandemic responses: from epidemiological modeling to vaccine development.","authors":"Mayur Suresh Gawande, Nikita Zade, Praveen Kumar, Swapnil Gundewar, Induni Nayodhara Weerarathna, Prateek Verma","doi":"10.1186/s43556-024-00238-3","DOIUrl":"10.1186/s43556-024-00238-3","url":null,"abstract":"<p><p>Integrating Artificial Intelligence (AI) across numerous disciplines has transformed the worldwide landscape of pandemic response. This review investigates the multidimensional role of AI in the pandemic, which arises as a global health crisis, and its role in preparedness and responses, ranging from enhanced epidemiological modelling to the acceleration of vaccine development. The confluence of AI technologies has guided us in a new era of data-driven decision-making, revolutionizing our ability to anticipate, mitigate, and treat infectious illnesses. The review begins by discussing the impact of a pandemic on emerging countries worldwide, elaborating on the critical significance of AI in epidemiological modelling, bringing data-driven decision-making, and enabling forecasting, mitigation and response to the pandemic. In epidemiology, AI-driven epidemiological models like SIR (Susceptible-Infectious-Recovered) and SIS (Susceptible-Infectious-Susceptible) are applied to predict the spread of disease, preventing outbreaks and optimising vaccine distribution. The review also demonstrates how Machine Learning (ML) algorithms and predictive analytics improve our knowledge of disease propagation patterns. The collaborative aspect of AI in vaccine discovery and clinical trials of various vaccines is emphasised, focusing on constructing AI-powered surveillance networks. Conclusively, the review presents a comprehensive assessment of how AI impacts epidemiological modelling, builds AI-enabled dynamic models by collaborating ML and Deep Learning (DL) techniques, and develops and implements vaccines and clinical trials. The review also focuses on screening, forecasting, contact tracing and monitoring the virus-causing pandemic. It advocates for sustained research, real-world implications, ethical application and strategic integration of AI technologies to strengthen our collective ability to face and alleviate the effects of global health issues.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"1"},"PeriodicalIF":6.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}